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Backgrounds:

In adults, there is a high risk of recurrent TB after successful treatment, however limited data is available in children. The aim of this study was to determine burden and risk factors of TB recurrence in children.

Methods

Retrospective descriptive study of TB recurrence in children aged 0-13 years presenting with presumptive pulmonary TB in Cape Town, South Africa from March 2012 to November 2017. Recurrent TB is defined as >1 episode TB treatment (both confirmed or clinically diagnosed disease).

Results:

Data of 608 children were reviewed for TB recurrence, the median age was 16.7 months (interquartile range, IQR: 9.5-33.3), 324 male (53.3%) and 72 living with HIV (LHIV, 11.8%).

A total of 52/608 (8.4%) of all children had reported previous treatment for TB. Of these, 28 were treated again as TB cases, and 2 were excluded due to misdiagnosis of TB at previous episode. Recurrent TB was thus seen in 26/281 (9.3%) of current TB cases.

8/26 (30.8%) of children had the same TB contact as the previous episode. Current TB episode was confirmed in 11/26 (42.3%) with median time-lapsed since previous episode of 21 months (IQR: 16.3-45). Underlying comorbidities were seen in 19/26 (73.1%) of the children, all HIV infected and some with malnutrition (8/26) and chronic lung disease (3/26). Two thirds of children LHIV reported poor adherence to antiretrovirals (84.2%) and low CD4 counts.

Conclusions/Learning Points:

Recurrent TB was common in this young cohort of children with PTB. Children LHIV are at significantly higher risk for recurrent TB. More data is needed to identify other risk factors for recurrent TB and long-term follow up for repeated recurrence and post TB lung disease.

Figure 1: Identification of children with recurrent TB

Backgrounds:

Before the COVID-19 pandemic, we described an increase in tuberculosis (TB) notification rates at the Campania Region’s paediatric Reference Centre (CRRC). Since 2020, we observed a reduction in the incidence of TB, hence, we decided to compare TB incidence rates and disease severity in the period 2020-2021 to 2011-2019.

Methods

We conducted a prospective cohort study (Jan 1st 2011 to Dec 31st 2021) enrolling children <18 years who received diagnosis of TB at the CRRC. Yearly TB incidence rates were calculated dividing the number of new cases with the number of residents < 18 years in Campania. Disease severity was based on the need of oxygen support and the score proposed by Wiseman et al. according to localization (pulmonary and extrapulmonary) and/or cavitation.

Results:

Overall 154 children (48.1% male, median age 63 months, IQR 101.76) received diagnosis of TB, 142 in the period 2011-2019 with a significant increase in notification rates overtime (Fig). In 2020-2021, 12 new diagnoses were notified with a drop from 1.46/100.000 (95%CI, 0.84-2.37) in 2019 to 0.38 (95%CI, 0.1-0.96) in 2021. Two (17%) needed oxygen support. The number of cases classified as severe according to clinical score, was higher in the period 2020-2021 (5/12, 42%) compared with 2011-2019 (22/142, 15%), with 2/12 (17%) extrapulmonary and 2/12 (17%) cavitation.

Conclusions/Learning Points:

During 2020-2021 the CRRC registered a decrease in TB notification rates and an increase in the severity of the disease, compared with 2011-2019. The Stop TB Partnership suggested that COVID-19 could cause an excess of TB cases globally between 2020 and 2025. That rebound, in Campania, has not yet occurred likely because of the shift in medical attention from TB and the reallocation of human resources towards the pandemic effort.

Backgrounds:

The diagnosis of tuberculosis (TB) in children remains the biggest hurdle in overcoming the epidemic. The blood-based T cell marker for TB assay (TAM TB) characterizes TB-specific CD4+ T cells based on the expression of surface markers. This approach allows a differentiation between latently and actively infected TB patients.

Methods

RaPaed-TB is a diagnostic validation study conducted in five countries enrolling children suspected of having TB. Alongside a thorough clinical and microbiological workup, a number of new tests are being evaluated including the TAM TB. The latter is a flow-cytometry based assay using a standardized kit which gives a result within 16-24h. Data cleaning is underway; presented data are preliminary and totals differ.

Results:

In total, 974 participants were enrolled with an overall microbiological confirmation rate (PCR/culture) of 24.2% (236/974), sufficient information for clinical case definition was available for 732 children. Overall, more than 890 TAM TBs were performed at enrolment. Using culture as reference standard, early analyses show a modest sensitivity of 60.8% (95%CI 48.8-72.0) and specificity of 83.5% (95%CI 77.0-88.9) in the overall cohort, with superior performance in children <1 year with a sensitivity of 80.0% (95%CI 51.9-95.7) and specificity of 85.0% (95%CI 62.1-96.8). Logistic regression was performed to explore determinants of TAM TB accuracy, generating strong evidence of TST-positivity increasing the odds for true-positivity in reference standard positive children by 5.06 (95%CI 1.83-13.99, p=0.0018). Further analyses are ongoing, and results are to be presented.

Conclusions/Learning Points:

RaPaed-TB is one of the largest TB diagnostic validation studies comparing several new tests ever performed in children. Presented data indicate a promising performance of TAM-TB, especially in the very young children.